We are developing
new ways to investigate DNA and RNA structure.The method involves synthesizing nucleoside analogues that
contain a probe group.IR and NMR
spectroscopy is then employed to study the local environment around the probe
which has been incorporated into DNA.Probes investigated so far include nitrile (CN) and azide (N3)
groups (Figure 1).The vibrational
Stark effect can be used to measure the electric field if the Stark tuning rate
of the probe is known.We have
therefore collaborated with the Boxer
group at Stanford to determine the tuning rate of a number of IR probes.1We are now collaborating with Scott Brewer
in our department to further investigate the solvent and temperature dependence
of the IR absorption band of several of these probe-containing
nucleosides.An important
part of this collaboration is modeling our experimental results utilizing DFT
calculations.

In order to use NMR
spectroscopy to investigate DNA we are incorporating an 15N or 13C
label into the nitrile group.In
this way we can investigate the solvent and temperature dependence of 15N-NMR
and 13C-NMR chemical shifts of the probe.These results will be compared to the IR peak shifts we
observed and to DFT NMR shift calculations.

These nucleoside
projects are an outgrowth of our earlier work on silatranyl- and
germatranyl-nucleosides.2-4These atranes were designed to be transition state analogues for
phosphoryl transfer reactions.

Another project in
our group involves the synthesis of molecular knots.This work involves a novel Thread & Cut method for knot
formation.5Synthetic
targets include the world's smallest trefoil knot, the first non-DNA figure
eight knot, and a polyethylene trefoil knot (Figure 2).The current published record for the
smallest knot is an 80-atom trefoil prepared by the Sauvage group
in France.6Our small
knot targets range in size from 63 to 78 backbone atoms.The figure eight knot is a particularly
attractive target because of its unusual stereochemistry – it is a
topological rubber glove.If
successful, the figure eight knot produced will be only the second example of a
chemically achiral molecule with this property.Finally, the polyethylene trefoil knot target is of interest
because we can compare its polymer properties to that of linear and cyclic7
polyethylene.Further background
about this aspect of our work is given below in a description aimed at a
general audience.

We
gratefully acknowledge past support for our molecular knot research from Research Corporation and Franklin &
Marshall College.

Why synthesize molecular
knots?

Long, linear objects spontaneously form knots.Examples include electrical cords,
hair, and molecules such as DNA and polymers.How do knots affect the structure of a material?A knot is known to weaken a rope and
when stretched the breaking point is always at the entrance to the knot.Theoretical calculations suggest that
the same is true of knotted polymer molecules, but this has never been tested
experimentally.Furthermore,
calculations strongly suggest that minute quantities of knots spontaneously
form when polymers such as polyethylene are synthesized.Polyethylene is perhaps the most
important plastic with an annual production of 40 million tons.Milk bottles, grocery bags, and pipes
are made of polyethylene.The goal
of one of our projects is to prepare a knotted version of a polyethylene
molecule and test its properties.Thus, the knowledge gained in this work may eventually address the issue
of why some grocery bags weaken and split open.

Polyethylene comes in different forms, but the basic structure is
a long linear chain of carbon atoms, each with two hydrogen atoms
attached.Recently, Noble Laureate
Bob Grubbs of Caltech
prepared and patented a cyclic version of polyethylene.7This version has unusual properties
that may prove useful.In terms of
knotted polyethylene, this molecule is a chemical Holy Grail.Frisch and Wasserman8 first
discussed it in 1961 and as recently as 1999 Sauvage et al. stated that, "the properties of a pure polymethylene
knotted ring should be fascinating, although the synthesis of such a compound
seems to be presently out of reach."9